João Lemos

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis

IMPORTANCE The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.

Neuro-Ophthalmological Emergencies.

Neuro-ophthalmological emergencies constitute vision or life-threatening conditions if diagnosis and treatment are not promptly undertaken. Even with immediate therapy, these clinical entities carry a high rate of morbidity. They may present with diplopia, visual loss, and/or anisocoria. Arteritic anterior ischemic optic neuropathy is an ominous condition, which can cause permanent and severe vision loss, stroke, or aortic dissection, requiring immediate steroid therapy. Pituitary apoplexy may go unnoticed if only computed axial tomography is performed. Diseases affecting the cavernous sinus and orbital apex region, such as cavernous sinus thrombosis or mucormycosis, can give rise to simultaneous vision loss and diplopia and, if not treated, may extend to the brain parenchyma causing permanent neurological sequela. An isolated third nerve palsy may be the harbinger of a cerebral aneurysm, carrying a significant risk of mortality. Horner syndrome can be the initial presentation of a carotid dissection, an important cause of stroke in the young adult. The neurohospitalist should be familiar with the workup and management of neuro-ophthalmological emergencies.

Prognosis of Ocular Myasthenia Gravis: Retrospective Multicenter Analysis

PURPOSE To calculate the rate and timing of conversion from ocular myasthenia gravis to generalized myasthenia gravis. DESIGN Retrospective multicenter analysis. SUBJECTS Patients included in the study were diagnosed with ocular myasthenia gravis without the presence of generalized disease at onset. METHODS We conducted a retrospective multicenter analysis. We reviewed charts of 158 patients who met diagnostic criteria for ocular myasthenia gravis. Patients were divided into 2 subgroups: an immunosuppressant treatment group and a nonimmunosuppressant treatment group. Timing of conversion to generalized disease and duration of follow-up also was evaluated. Additional data such as clinical symptoms at presentation, laboratory test results, and chest imaging results also were recorded. MAIN OUTCOME MEASURES Conversion rates to generalized myasthenia at 2 years, effect of immunosuppression on conversion, and timing of conversion. RESULTS The 158-patient cohort included 76 patients who received immunosuppressant therapy; the remaining 82 patients did not. The overall conversion rate to generalized disease was 20.9%. At 2 years, generalized myasthenia developed in 8 of 76 patients in the treated group and in 15 of 82 patients in the nonimmunotherapy group (odds ratio, 0.52; 95% confidence interval, 0.20-1.32). Median time for conversion to generalized disease was 20 months in the nonimmunosuppressant group and 24 months in the immunosuppressant group. Conversion occurred after 2 years of symptom onset in 30% of patients. CONCLUSIONS Conversion rates from ocular to generalized myasthenia gravis may be lower than previously reported both in immunosuppressed and nonimmunosuppressed patients. A subset of patients may continue to convert to generalized disease beyond 2 years from onset of symptoms, and close monitoring should be continued.

Distinct functional properties of the vertical and horizontal saccadic network in Health and Parkinson's disease: An eye-tracking and fMRI study.

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinsons disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.

Supranuclear eye movement disorders.

Purpose of review This work reviews supranuclear ocular motor disorders, highlighting new data published during the past year. Recent findings Perceptional adaptative mechanisms may explain recent research concerning the discrepancy between objective measurement of saccade abnormalities and their putative functional visual impairment. Eye movement classes seem to be selectively disrupted by different neurodegenerative disorders. Deep brain stimulation in Parkinsons disease patients may improve pursuit deficits, highlighting the role of basal ganglia in the control of smooth pursuit. Subcortical optokinetic pathways seem to play an important role in maintaining the monocular nasotemporal optokinetic asymmetry seen in patients with infantile esotropia. Vergence–vestibular interaction has been further delineated in patients with idiopathic bilateral vestibular failure. Pharmacological treatment of central vestibular disorders with 4-aminopyridine has been extended to patients with ataxia-telangiectasia in whom it seems to reduce slow-phase velocity of nystagmus. Summary Recent data derived from anatomic and functional imaging studies are providing new insights into supranuclear ocular motor circuitry. Novel pharmacological and surgical therapies may have future implications in visual and vestibular rehabilitation of patients with supranuclear eye movement disorders.

Visual Cortex Plasticity Following Peripheral Damage To The Visual System: fMRI Evidence

Over the last two decades, functional magnetic resonance imaging (fMRI) has become a powerful research method to investigate cortical visual plasticity. Abnormal fMRI response patterns have been occasionally detected in the visually deprived cortex of patients with bilateral retinal diseases. Controversy remains whether these observations indicate structural reorganization of the visual cortex or unmasking of previously silent cortico-cortical connections. In optic nerve diseases, there is weak evidence showing that early visual cortex seems to lack reorganization, while higher-order visual areas undergo plastic changes which may contribute to optimise visual function. There is however accumulating imaging evidence demonstrating trans-synaptic degeneration of the visual cortex in patients with disease of the anterior visual pathways. This may preclude the use of restorative treatments in these patients. Here, we review and update the body of fMRI evidence on visual cortical plasticity.

Clinical utility and assessment of cyclodeviation

Purpose of review This article reviews and updates basic concepts, diagnosis and treatment of cyclotorsion. Recent findings Cyclodeviation in congenital superior oblique palsy (SOP) seems to correlate with the extent of superior oblique muscle hypoplasia. Genetic polymorphisms such as PHOX2B polymorphism, considered to be risk factors for congenital fibrosis of the extraocular muscles, may play a role in SOP and consequently in cyclotorsion. Two components of the ocular tilt reaction, ocular torsion and tilt of subjective visual vertical, seem to share similar sites of impairment in the brainstem. Harada-Ito surgery continues to be the procedure of choice in patients with isolated cyclodeviation, evidencing better outcome if less than 10° of preoperative excyclotorsion and preoperative fusion exist. Ocular torsion is not infrequent in patients with intermittent exotropia, especially in the most exo-deviated eye, emphasizing a possible role in pathogenesis. A new device for the assessment of dynamic torsion during ocular counter roll response using after-image has been described. Similarly, a new method to measure objective ocular torsion using retinal arcade tilt as a reference has been proposed. Finally, torsional data transformation such as the sum of angles of excyclodeviation, rather than using the angle of excyclodeviation of the paretic eye, is becoming increasingly popular among studies on torsion. Summary Exciting developments on ocular torsion have been described recently, and new ways to access and interpret ocular torsion have been devised as well.

Characterizing Parkinson’s Disease Speech by Acoustic and Phonetic Features

This study intends to identify acoustic and phonetic characteristics of the speech of Parkinson’s Disease (PD) patients, usually manifesting hypokinetic dysarthria. A speech database has been collected from a control group and from a group of patients with similar PD severity, but with different degrees of hypokinetic dysarthria. First and second formant frequencies of vowels in continuous speech were analyzed. Several classifiers were built using phonetic features and a range of acoustic features based on cepstral coefficients with the objective of identifying hypokinetic dysarthria. Results show a centralization of vowel formant frequencies for PD speech, as expected. However, some of the features highlighted in literature for discriminating PD speech were not always found to be statistically significant. The automatic classification tasks to identify the most problematic speakers resulted in high precision and sensitivity by using two formant metrics simultaneously and in even higher performance by using acoustic dynamic parameters.

Cortical control of vertical and horizontal saccades in progressive supranuclear palsy: An exploratory fMRI study

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Downbeat nystagmus elicited by eyelid closure.

We describe a patient with downbeat nystagmus (DBN) evoked only by eye closure. Brain and spinal cord magnetic resonance imaging revealed a T2 paramedian lesion in the left lower basis pontis and other white matter lesions consistent with multiple sclerosis. One potential mechanism for DBN in this case involves transverse ephaptic spread of excitation from areas that subserve coordinated lid closure to the decussating ventral tegmental tract.